The hearts of bivalved molluscs are structurally and functionally analogous to those of vertebrates, and are favorable model systems for studying the general mechanisms underlying rhythmical activity in cardiac muscle. This investigation of molluscan hearts will focus on two agents which profoundly modify rhythmicity: Peak C and 5-hydroxytryptamine (5HT). Peak C, extracted from molluscan central ganglia, is a tetrapeptide. It is a cardioexcitor agent initiating, regularizing or augmenting the beat of molluscan hearts. The pharmacology of Peak C on molluscan muscles, but especially hearts, will now be studied. Vertebrate visceral muscle will also be tested. Finally, the subcellular distribution of Peak C in molluscan ganglia, and its systematic distribution in the phylum, will be determined. Since, in contrast to Peak C, the effects of 5HT on molluscan hearts is variable, the actions of this drug will be compared on the hearts of 4 animals: Mercenaria mercenara, Mytilus edulis, and two subspecies of Modiolus demissus. These myocardia vary in their responses to 5HT, and in the ionic dependence of their spontaneous excitation. This investigation will focus on the calcium compartments involved in 5HT action and will proceed along 3 lines. Organ bath experiments will be carried out to determine the effects of lanthanum, caffeine and low calcium on the 5HT modification of rhythmicity. The effects of these same agents on Ca45 ion distribution and movement will be determined in uptake and efflux experiments. Finally, an attempt will be made to identify the morphological sites of calcium accumulation by the application of electron microscopical techniques. BIBLIOGRAPHIC REFERENCES: Higgins, William J. (1974). Intracellular actions of 5-hydroxytryptamine on the bivalve myocardium. I. Adenylate and guanylate cyclases. J. Exp. Zool. 190:99-110. Higgins, W.J. and Greenberg, M.J. (1974) Intracellular actions of 5-hydroxytryptamine on the bivalve myocardium. II. Cyclic nucleotide-dependent protein kinases and microsomal calcium uptake. J. Exp. Zool. 190:305-316.